A New Multi-objective Approach for Molecular Docking Based on RMSD and Binding Energy
Ligand-protein docking is an optimization problem based on predicting the position of a ligand with the lowest binding energy in the active site of the receptor. Molecular docking problems are traditionally tackled with single-objective, as well as with multi-objective approaches, to minimize the binding energy. In this paper, we propose a novel multi-objective formulation that considers: the Root Mean Square Deviation (RMSD) difference in the coordinates of ligands and the binding (intermolecular) energy, as two objectives to evaluate the quality of the ligand-protein interactions. To determine the kind of Pareto front approximations that can be obtained, we have selected a set of representative multi-objective algorithms such as NSGA-II, SMPSO, GDE3, and MOEA/D. Their performances have been assessed by applying two main quality indicators intended to measure convergence and diversity of the fronts. In addition, a comparison with LGA, a reference single-objective evolutionary algorithm for molecular docking (AutoDock) is carried out. In general, SMPSO shows the best overall results in terms of energy and RMSD (value lower than 2Å for successful docking results). This new multi-objective approach shows an improvement over the ligand-protein docking predictions that could be promising in in silico docking studies to select new anticancer compounds for therapeutic targets that are multidrug resistant.
KeywordsMolecular docking Multi-objective optimization Nature inspired metaheuristics Algorithm comparison
This work is partially funded by Grants TIN2011-25840 (Ministerio de Ciencia e Innovación) and P11-TIC-7529 and P12-TIC-1519 (Plan Andaluz de Investigación, Desarrollo e Innovación). This article is based upon work from COST Action CA15140, supported by COST (European Cooperation in Science and Technology).
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